Effectiveness of intraoral stents in reducing oral adverse events during radiotherapy for maxillary or nasal cavity malignant tumors.

PURPOSE: Many patients experience oral adverse events during head and neck cancer radiotherapy (RT). The methods of management of such events are under debate. One such technique is the intraoral stent (IOS) technique, which removes normal tissue from the irradiation field. This retrospective study examined the factors associated with the occurrence of oral mucositis (OM) and dysgeusia and the efficacy of IOSs in preventing them. METHODS: Twenty-nine patients who underwent RT in the maxilla or nasal cavity between 2016 and 2022 were included. They were investigated for background characteristics, treatment factors (IOS and dose-volume histogram), and oral adverse events (OM and dysgeusia). RESULTS: Significant risk factors for the incidence of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) OM were the non-use of IOSs (p = 0.004) and diabetes (p = 0.025). A significant risk factor for the incidence of grade ≥ 1 dysgeusia was concomitant chemotherapy (p = 0.019). The radiation dose to the tongue was significantly lower in the IOS group than in the non-IOS group. CONCLUSION: Our findings suggest that the use of an IOS during RT reduces the severity of OM by reducing irradiation to the tongue. Therefore, the use of an IOS is recommended during RT performed in the maxilla or nasal cavity.

Association between dental extraction after radiotherapy and osteoradionecrosis: A multi-centre retrospective study.

OBJECTIVE: Radiotherapy (RT) carries a substantial risk for the development of osteoradionecrosis (ORN) of the jaw. This study was performed to investigate the relationship between dental extractions after RT and the development of ORN. MATERIAL AND METHODS: Thirty-two patients with head and neck cancer who underwent tooth extraction after RT were investigated for correlations between the development of ORN and various factors. RESULTS: Postextraction ORN was diagnosed in 12 (12.1%) teeth of 9 patients. The RT dose against the site of tooth extraction was 62.0 and 37.4 Gy in the ORN and Non-ORN groups, respectively (p < .001). The duration from RT to tooth extraction was 41.2 and 28.2 months in the ORN and Non-ORN groups, respectively (p = .025). Tooth extraction was significantly associated with ORN in patients with a high RT dose against the site (odds ratio = 1.231) and a longer duration of time from RT (odds ratio = 1.084). CONCLUSIONS: Extraction of non-restorable teeth and those with a poor prognosis should not necessarily be postponed even when patients are undergoing RT. However, clinicians should pay special attention to postoperative management after tooth extraction in patients with a high RT dose and longer time from RT.

Bevacizumab-Associated Implant Presence-Triggered Osteonecrosis: A Case Report and Literature Review.

The effect of bevacizumab-related osteonecrosis of the jaw on previously osseointegrated dental implants has not been adequately studied. Here, we report a case of osteonecrosis of the jaw detected around dental implants placed before bevacizumab therapy. A 66-year-old woman undergoing bevacizumab therapy for metastatic triple-negative breast cancer developed malocclusion after buccal gingival swelling and pain in the #18, #19, and #20 tooth region. The patient visited a local dental clinic, where existing implants in relation to #19 and #20 were removed. Subsequently, the patient visited our department, and intraoral examination revealed necrotic bone in the region corresponding to #19 and #20. Radiographic examination showed a pathologic fracture in this region that was considered to result from osteonecrosis of the jaw. Bevacizumab therapy was suspended temporarily until the acute inflammation had subsided. In addition, treatment with antibacterial agents and conservative surgery was considered. Complete soft tissue coverage was observed 14 days after surgery. In recent years, the number of patients receiving bevacizumab treatment has increased. Because bevacizumab-related osteonecrosis of the jaw could occur around previously osseointegrated dental implants as well, this case report suggests an effective treatment regimen based on a combination of antibacterial agents and conservative surgery.

Oral risk factors associated with medication-related osteonecrosis of the jaw in patients with cancer.

INTRODUCTION: Bone-modifying agents (BMAs) are indispensable to cancer therapy. However, the number of patients with medication-related osteonecrosis of the jaw (MRONJ) is increasing according to the BMA administration. Oral factors predisposing to development of MRONJ are receiving attention, and oral management is recommended for prevention of MRONJ; however, the strategy and criteria have not yet been established. Therefore, we investigated the oral risk factors associated with MRONJ development in this study. MATERIALS AND METHODS: A retrospective study was carried out on 398 cancer patients who had received oncological-dose BMAs between 2007 and 2018; general health factors, demographic, and dental factors were examined along with MRONJ development in all the patients. The cumulative occurrence rate of MRONJ was calculated using a Kaplan-Meier analysis. Clinical factors were analyzed using the Cox regression analysis. RESULTS: MRONJ occurred in 42 of the 398 patients. The cumulative MRONJ incidence rates were 4.5, 12.9, 17.7, and 21.6% at 1, 2, 3, and 4 years, respectively. Age (p = 0.038), male sex (p = 0.002), initiation of dental interventions before BMA administration (p = 0.020), alveolar bone loss involving more than half the root (p < 0.001), and torus mandibularis (p < 0.001) were significantly associated with MRONJ. CONCLUSIONS: Our findings suggest that patients with alveolar bone loss involving more than half the root on panoramic radiographs and torus mandibularis carry a high risk of MRONJ development. Early dental intervention before BMA administration and oral management during the treatment are important for preventing MRONJ.

Does inflammatory dental disease affect the development of medication-related osteonecrosis of the jaw in patients using high-dose bone-modifying agents?

OBJECTIVES: High-dose bone-modifying agents (BMAs), such as bisphosphonates and denosumab, are essential for the treatment of cancer patients with bone metastases. The incidence of medication-related osteonecrosis of the jaw (MRONJ) is increasing. Inflammatory dental diseases could lead to MRONJ, and hence, they should be managed appropriately. Tooth extractions are commonly advised to prevent dental inflammation; however, the accurate indications for tooth extractions before starting BMA therapy have not been established. Hence, we assessed teeth with inflammatory dental diseases to identify indicators for prophylactic extraction before starting BMA therapy. MATERIALS AND METHODS: We included 745 teeth with inflammatory dental diseases of 212 cancer patients on high-dose BMA therapy. We assessed the relationship between inflammatory dental disease and risk of MRONJ development. Multivariate Cox regression analysis was used for statistical analysis. The cumulative occurrence rate of MRONJ was calculated using the Kaplan-Meier method. RESULTS: MRONJ occurred in 43 of 745 teeth. Teeth characteristics significantly correlated with MRONJ occurrence were mandible (p = 0.009), molar region (p = 0.005), radiopaque changes in bone surrounding the root on orthopantograms obtained at patients' first visits (p < 0.001), and tooth extractions after starting BMA therapy (p < 0.001). CONCLUSIONS: Radiopaque changes in bone surrounding the root are an important radiographic finding that indicates the need for prophylactic tooth extractions before starting BMA therapy. CLINICAL RELEVANCE: Our results suggest that the prophylactic extraction of teeth with radiopaque changes in bone surrounding the root before starting BMA therapy could prevent the onset of MRONJ.

Drug holiday clinical relevance verification for antiresorptive agents in medication-related osteonecrosis cases of the jaw.

Treatment strategies of medication-related osteonecrosis of the jaw (MRONJ) are controversial. Recently, surgical treatment has been reported as superior to nonsurgical treatment, but the contribution discontinued antiresorptive agent use during MRONJ treatment remains unclear. This study aimed to evaluate the efficacy of drug holidays and treatment strategies in MRONJ cases. Four-hundred and twenty-seven patients with MRONJ treated at nine hospitals from 2009 to 2017 were included in this multicenter retrospective study. Multivariate Cox regression analysis showed that the primary disease (osteoporosis or malignant tumor), diabetes, serum albumin, and treatment method (surgical or nonsurgical) were significantly correlated with the cure rate. The cumulative 1-year cure rates in the surgical and nonsurgical treatment groups were 64.7% and 18.2%, respectively. However, discontinuing antiresorptive agents did not influence the treatment outcome in the cohort overall, or in 230 patients after performing propensity score matching among the discontinuation and continuation groups. When stratifying by treatment method, antiresorptive agent discontinuation significantly increased the cure rate in patients with osteoporosis who underwent nonsurgical treatment. In patients with malignant tumors undergoing nonsurgical therapy, discontinuing the antiresorptive agent was associated with a better treatment outcome, but not with statistical significance. In contrast, drug holidays showed no effect on improving outcomes in patients with both osteoporosis and malignant tumors who underwent surgical therapy. Thus, regardless of the primary disease, discontinuing antiresorptive agents during treatment for MRONJ may not be necessary and may be helpful in some cases. Future prospective trials should examine this question further.

Prevalence of and risk factors for postoperative hemorrhage after lower third molar extraction on warfarin therapy: a multicenter retrospective study in Japan.

Postoperative hemorrhage after tooth extraction is a critical and clinically important issue for clinicians and patients receiving anticoagulants. The purpose of the present study was to investigate the prevalence of and risk factors for postoperative hemorrhage after lower third molar extraction in Japanese patients receiving warfarin therapy. A total of 142 patients who underwent lower third molar extraction between January 2010 and December 2016 were included, and their medical records were retrospectively reviewed. The prevalence of and risk factors for postoperative hemorrhage were investigated. The prevalence of postoperative hemorrhage after lower third molar extraction was significantly higher in patients receiving warfarin than in healthy subjects (21.8% vs 0.7%, P < 0.001). The cutoff value for PT-INR was 2.11 based on a receiver-operating characteristic analysis. A multivariate analysis indicated that an elevated PT-INR value [hazard ratio (HR) 3.798, 95% confidence interval (CI) 1.400-10.467, P < 0.01], preoperative antibiotic administration (HR 4.434, 95% CI 1.591-14.775, P < 0.01), difficulties with intraoperative hemostasis (HR 16.298, 95% CI 2.986-110.677, P < 0.01), and higher serum creatinine levels (HR 7.465, 95% CI 1.616-39.576, P < 0.05) are significant predictors of postoperative hemorrhage after lower third molar extraction. Multivariate correlations were observed between risk factors including an elevated PT-INR value, preoperative antibiotic administration, and higher serum creatinine levels, and postoperative hemorrhage after lower third molar extraction in patients receiving warfarin therapy. Clinicians need to consider these risk factors for postoperative hemorrhage after the lower third molar extraction and monitor PT-INR in patients receiving warfarin therapy.

Measurement of Thickness at the Inferior Border of the Mandible Using Computed Tomography Images: A Retrospective Study including 300 Japanese Cases.

Vascularised fibular free flaps are integral to reconstructive surgery for head and neck tumours. We investigated the morphological characteristics of the mandible to improve the incidence of plate-related complications after surgery. Using standard radiological software, thickness measurements of the inferior or posterior margin of the mandible were obtained from computed tomography images of 300 patients at seven sites: (1) mandibular symphysis, (2) midpoint between the mandibular symphysis and mental foramen, (3) mental foramen, (4) midpoint between the mental foramen and antegonial notch, (5) antegonial notch, (6) mandibular angular apex (gonion), and (7) neck lateral border of the dentate cartilage. Relationships between age, sex, height, weight, the number of remaining teeth in the mandible, and the thickness of each mandible were also investigated. Measurement point 1 had the largest median mandibular thickness (11.2 mm), and measurement point 6 had the smallest (5.4 mm). Females had thinner measurements than males at all points, with significant differences at points 1, 2, 3, 4, and 7 (p < 0.001). Age and number of remaining teeth in the mandible did not correlate with mandibular thickness; however, height and weight correlated at all points except point 6. Thickness measurements obtained at the sites provide a practical reference for mandibular reconstruction. Choosing the fixation method based on the measured thickness of the mandible at each site allows for sound plating.

Risk factors for osteoradionecrosis of the jaw in patients with oral or oropharyngeal cancer: Verification of the effect of tooth extraction before radiotherapy using propensity score matching analysis.

Background/purpose: Osteoradionecrosis of the jaw (ORN) often occurs in patients with head and neck cancer undergoing radiotherapy (RT). It has been recommended to extract the tooth before RT that may become source of infection, but in recent years, some investigators have reported that tooth extraction before RT increase the risk of developing ORN and therefore should be avoided. The purpose of the study is to evaluate the risk factors for ORN including tooth extraction before RT. Materials and methods: This was a retrospective study of 366 patients with oral or oropharyngeal cancer who underwent RT of 50 Gy or more at six university hospitals, with follow-up of at least six months post-RT. The relationship between each factor and ORN incidence was analyzed using the Cox proportional hazard model. Results: Periapical lesions, more than 50% loss of alveolar bone, and tooth extraction after RT significantly correlated with ORN. Intensity-modulated RT showed a lower incidence than three-dimensional conformal RT, although not statistically different. Tooth extraction before RT significantly reduced ORN incidence, after adjusting the background factors using propensity score matching. Conclusion: In patients with oral or oropharyngeal cancer who underwent RT, periapical lesions, more than 50% loss of alveolar bone, and tooth extraction after RT significantly increased the risk for ORN. Infected tooth extraction before RT significantly reduced the risk.

Perioperative oral care can prevent surgical site infection after colorectal cancer surgery: A multicenter, retrospective study of 1,926 cases analyzed by propensity score matching.

BACKGROUND: Surgical site infection is a common postoperative complication of colorectal cancer surgery, and surgical site infection increases medical costs, prolongs hospitalization, and worsens long-term prognosis. Perioperative oral care has been reported to be effective in preventing postoperative pneumonia, although there are only a few reports on its effectiveness in preventing surgical site infection. This study aimed to determine the role of perioperative oral care in surgical site infection prevention after colorectal cancer surgery. METHODS: In this study, 1,926 patients with colorectal cancer from 8 institutions were enrolled; 808 patients (oral care group) received perioperative oral care at the hospital's dental clinic, and 1,118 (control group) did not receive perioperative oral care. The data were matched by propensity score to reduce bias. Ultimately, a total of 1,480 patients were included in the analysis. RESULTS: The incidence of surgical site infection was significantly lower in the oral care group than in the control group (8.4% vs 15.7%, P < .001). Multivariate logistic regression analysis revealed 4 independent risk factors for surgical site infection: low albumin level, rectal cancer, blood loss, and lack of perioperative oral care. Lack of perioperative oral care had an odds ratio of 2.100 (95% confidence interval 1.510-2.930, P < .001). CONCLUSION: These results suggest that perioperative oral care can reduce the incidence of surgical site infection after colorectal cancer resection. Perioperative oral care may have an important role in the future perioperative management of colorectal cancer as a safe and effective method of surgical site infection prevention, although further validation in prospective studies is needed.

Prevalence of and risk factors for postoperative complications after lower third molar extraction: A multicenter prospective observational study in Japan.

Lower third molar extraction is the most common surgical treatment among routine dental and oral surgical procedures. while the surgical procedures for lower third molar extraction are well established, the difficulty of tooth extraction and the frequency of postoperative complications differ depending on the patient's background. To establish a management protocol for the lower third molars, the prevalence of and risk factors for postoperative complications after lower third molar extraction were investigated in a large number of Japanese patients in a multicenter prospective study. During 6 consecutive months in 2020, 1826 lower third molar extractions were performed at the 20 participating institutions. The medical records of the patients were reviewed, and relevant data were extracted. The prevalence of and risk factors for postoperative complications were analyzed. The prevalence of postoperative complications after lower third molar extraction was 10.0%. Multivariate analysis indicated that age (≤32 vs >32, odds ratio [OR]: 1.428, 95% confidence interval [95% CI]: 1.040-1.962, P < .05), the radiographic anatomical relationship between the tooth roots and mandibular canal (overlapping of the roots and canal vs no close anatomical relationship between the roots and the superior border of the canal, OR: 2.078, 95% CI: 1.333-3.238, P < .01; overlapping of the roots and canal vs roots impinging on the superior border of the canal, OR: 1.599, 95% CI: 1.050-2.435, P < .05), and impaction depth according to the Pell and Gregory classification (position C vs position A, OR: 3.7622, 95% CI: 2.079-6.310, P < .001; position C vs position B, OR: 2.574, 95% CI: 1.574-4.210, P < .001) are significant independent risk factors for postoperative complications after lower third molar extraction. These results suggested that higher age and a deeply impacted tooth might be significant independent risk factors for postoperative complications after lower third molar extraction.

[Dental injury associated with general anesthesia and the preventive measures].

BACKGROUND: It is generally recognized that dental injury during general anesthesia is an important problem. We retrospectively evaluated the profiles of dental injuries during general anesthesia and associated factors for the development of dental injury. METHODS: From January 1999 to December 2008, all medical records of the patients with dental injury during general anesthesia were reviewed. RESULTS: Of 30,845 patients who underwent general anesthesia in the period, the dental injury developed in 110 patients (0.36%) during general anesthesia. The incidence of dental injury was higher in patients above 60 years of age, The patients who had received mouth guards had significantly lower incidence of dental injury compared with those without mouth guards (0.06% vs. 0.37%, P < 0.05). The left upper incisors were involved most commonly in the development of dental injury, and the timing of dental injury was most frequent at the time of tracheal intubation.

Enumerated sparse extraction of important surgical planning features for mandibular reconstruction.

Because implicit medical knowledge and experience are used to perform medical treatment, such decisions must be clarified when systematizing surgical procedures. We propose an algorithm that extracts low-dimensional features that are important for determining the number of fibular segments in mandibular reconstruction using the enumeration of Lasso solutions (eLasso). To perform the multi-class classification, we extend the eLasso using an importance evaluation criterion that quantifies the contribution of the extracted features. Experiment results show that the extracted 7-dimensional feature set has the same estimation performance as the set using all 49-dimensional features.

Study of Treatment Methods for Surrounding Soft Tissues of Implants Following Mandibular Reconstructions with Fibula-Free Flaps.

In maxillofacial reconstruction implant treatment, unsatisfactory soft tissue treatment of the area around the implant may lead to inflammation. As a result, appropriate soft tissue treatment is critical. To the best of our knowledge, there are no studies that compare the different tissue treatment methods available. Hence, in this study, we compare three soft tissue treatment methods around implants after mandibular reconstruction is achieved with a fibula-free flap. Out of 33 patients who underwent mandible reconstruction using fibula-free flaps between 2006 and 2015, 5 were selected for this study. A total of 17 implants were used for treatment by the final prosthetics of the five patients. Three soft tissue treatment methods with free gingival graft (FGG) were evaluated, namely, installing a splint in a modified abutment to protect the wounded area during a palatal mucosa transplant (method 1), installing a splint or dentures to a locator abutment (method 2), and the use of screw-in fixed dentures (method 3). The method that could guarantee the widest keratinized mucosa was the screw-in fixed denture method. The results of our study indicated that employing screw-in fixed dentures for FGG may be a useful soft tissue treatment for mandible reconstruction implants.

Automated Planning With Multivariate Shape Descriptors for Fibular Transfer in Mandibular Reconstruction.

OBJECTIVE: This paper introduces methods to automate preoperative planning of fibular segmentation and placement for mandibular reconstruction with fibular flaps. METHODS: Preoperative virtual planning for this type of surgery has been performed by manual adjustment of many parameters, or based upon a single feature of the reconstruction. We propose a novel planning procedure formulated as a nonconvex minimization problem of an objective function using the multilateral shape descriptors. RESULTS: A retrospective study was designed and 120 reconstruction plans were reproduced using computed tomography images with oral surgeons. The proposed automated planning model was quantitatively compared with both the existing model and the surgeons' plans. CONCLUSION: The results show that the developed framework attains stable automated planning that agrees with the surgeons' decisions. SIGNIFICANCE: This method addresses tradeoff problems between symmetric reconstruction and restoration of the native contour of the mandible.

Evaluation of the Treatment Strategies for Medication-Related Osteonecrosis of the Jaws (MRONJ) and the Factors Affecting Treatment Outcome: A Multicenter Retrospective Study with Propensity Score Matching Analysis.

Medication-related osteonecrosis of the jaw (MRONJ) is an adverse event that may inhibit the treatment of primary disease and remarkably influence the patient's quality of life. The treatment methods for MRONJ, nonsurgical and surgical, are controversial, with no agreement as to which method provides the best outcome and should therefore be recommended. This multicenter retrospective study aimed to investigate the treatment methods and outcome in a large number of patients with MRONJ in Japan, utilizing propensity score matching analysis. A total of 361 patients with MRONJ, at eight hospitals, were registered in this study retrospectively. Various demographic and treatment-related variables were examined and analyzed to determine their correlation with the treatment outcome. After propensity score matching for treatment methods (nonsurgical versus surgical treatment), 176 patients were analyzed by logistic regression. It was shown that those with low-dose administration of an antiresorptive agent and surgical treatment had better outcomes. Furthermore, in 159 patients who underwent surgical treatment, those who underwent extensive surgery experienced significantly better treatment outcomes than those who underwent conservative surgery. This is the first study to compare treatment methods for MRONJ using propensity score matching analysis. The results indicated that extensive surgical treatment should be performed as first-choice therapy for patients with MRONJ. © 2017 American Society for Bone and Mineral Research.

Relationship between dental status and development of osteoradionecrosis of the jaw: a multicenter retrospective study.

OBJECTIVE: Osteoradionecrosis of the jaw is a serious late adverse event in patients with head and neck cancer undergoing radiotherapy. The aim of this study is to investigate the relationship between dental status and development of osteoradionecrosis. STUDY DESIGN: Multicenter, retrospective observational study. A total of 392 patients with head and neck cancer who underwent radiotherapy were investigated for correlations between the development of osteoradionecrosis and various factors. The cumulative occurrence rate of osteoradionecrosis was calculated by the Kaplan-Meier method and analyzed by Cox regression and log-rank test. RESULTS: Osteoradionecrosis developed in 30 of 392 patients. In 23 patients, osteoradionecrosis occurred in the mandibular molar region. A univariate analysis showed that oral or oropharyngeal cancer, jaw radiotherapy dose exceeding 50 Gy, periapical periodontitis, and tooth extraction after radiotherapy were significantly correlated with the occurrence of osteoradionecrosis. Among these, oral and oropharyngeal cancer, periapical periodontitis, and tooth extraction after radiotherapy were significant independent risk factors by multivariate analysis. Further, caries that occurred after radiotherapy and progressed rapidly, resulting in periapical periodontitis, carious stump, or extraction, was a major cause of osteoradionecrosis. CONCLUSION: Extraction of mandibular molars with periapical periodontitis before radiotherapy and strict dental management after radiotherapy may reduce the risk of osteoradionecrosis.

Sparse shape model for fibular transfer planning in mandibular reconstruction.

In this paper, we propose an automated preoperative planning method that estimates a plan fitted to the data of a new patient using a planned dataset of previous patients. Although mandibular reconstruction with fibular segments needs preoperative planning for the precise placement of segments, recent interactive planning software cannot secure objectivity of the planning and time-consuming trial-and-error processes are required. The proposed method employs sparse shape modeling; in this modeling, we select a subset of the data from a prepared preoperative planning dataset to make an example or instance of reconstruction via a linear combination of the data. We conduct experiments using the dataset planned by medical doctors and compare the instance estimated by the proposed method to the manual placement by these doctors.

Statistical Analysis of Interactive Surgical Planning Using Shape Descriptors in Mandibular Reconstruction with Fibular Segments.

This study was performed to quantitatively analyze medical knowledge of, and experience with, decision-making in preoperative virtual planning of mandibular reconstruction. Three shape descriptors were designed to evaluate local differences between reconstructed mandibles and patients' original mandibles. We targeted an asymmetrical, wide range of cutting areas including the mandibular sidepiece, and defined a unique three-dimensional coordinate system for each mandibular image. The generalized algorithms for computing the shape descriptors were integrated into interactive planning software, where the user can refine the preoperative plan using the spatial map of the local shape distance as a visual guide. A retrospective study was conducted with two oral surgeons and two dental technicians using the developed software. The obtained 120 reconstruction plans show that the participants preferred a moderate shape distance rather than optimization to the smallest. We observed that a visually plausible shape could be obtained when considering specific anatomical features (e.g., mental foramen. mandibular midline). The proposed descriptors can be used to multilaterally evaluate reconstruction plans and systematically learn surgical procedures.

Volumetric fibular transfer planning with shape-based indicators in mandibular reconstruction.

In preoperative planning for mandibular reconstructive surgery, it is necessary to determine the osteotomy lines for fibular shaping and the proper placement of fibular segments in the mandible. Although virtual surgical planning has been utilized in preoperative decision making, current software designs require manual operation and a trial-and-error process to refine the reconstruction plan. We have developed volumetric fibular transfer simulation software that can quickly design a preoperative plan based on direct volume manipulation and quantitative comparison with the patient's original mandible. We propose three quantitative shape indicators-volume ratio, contour error, and maximum projection-for symmetrical lesions of the mandible, and have implemented a parallel computation algorithm for the semiautomatic placement of fibular segments. Using this virtual planning software, we conducted a retrospective study of the computed tomography data from nine patients. We found that combining direct volume manipulation with real-time local search of placement improved the applicability of the planning system to optimize mandibular reconstruction.